Century after pandemic, science takes its best shot at flu

Some victims felt fine in the morning and were dead by night. Faces turned blue as patients coughed up blood. Stacked bodies outnumbered coffins.

A century after one of history’s most catastrophic disease outbreaks, scientists are rethinking how to guard against another super-flu like the 1918 influenza that killed tens of millions as it swept the globe.

There’s no way to predict what strain of the shape-shifting flu virus could trigger another pandemic or, given modern medical tools, how bad it might be.

But researchers hope they’re finally closing in on stronger flu shots, ways to boost much-needed protection against ordinary winter influenza and guard against future pandemics at the same time.

“We have to do better and by better, we mean a universal flu vaccine. A vaccine that is going to protect you against essentially all, or most, strains of flu,” said Dr. Anthony Fauci of the National Institutes of Health.

Labs around the country are hunting for a super-shot that could eliminate the annual fall vaccination in favor of one every five years or 10 years, or maybe, eventually, a childhood immunization that could last for life.

Fauci is designating a universal flu vaccine a top priority for NIH’s National Institute of Allergy and Infectious Diseases. Last summer, he brought together more than 150 leading researchers to map a path. A few attempts are entering first-stage human safety testing.

Still, it’s a tall order. Despite 100 years of science, the flu virus too often beats our best defenses because it constantly mutates.

Among the new strategies: Researchers are dissecting the cloak that disguises influenza as it sneaks past the immune system, and finding some rare targets that stay the same from strain to strain, year to year.

“We’ve made some serious inroads into understanding how we can better protect ourselves. Now we have to put that into fruition,” said well-known flu biologist Ian Wilson of The Scripps Research Institute in La Jolla, California.

The somber centennial highlights the need.

Back then, there was no flu vaccine. It wouldn’t arrive for decades. Today vaccination is the best protection, and Fauci never skips his. But at best, the seasonal vaccine is 60 percent effective. Protection dropped to 19 percent a few years ago when the vaccine didn’t match an evolving virus.

If a never-before-seen flu strain erupts, it takes months to brew a new vaccine. Doses arrived too late for the last, fortunately mild, pandemic in 2009.

Lacking a better option, Fauci said the nation is “chasing” animal flu strains that might become the next human threat. Today’s top concern is a lethal bird flu that jumped from poultry to more than 1,500 people in China since 2013. Last year it mutated, meaning millions of just-in-case vaccine doses in a U.S. stockpile no longer match.

The NIH’s Dr. Jeffery Taubenberger calls the 1918 flu the mother of all pandemics.

He should know.

While working as a pathologist for the military, he led the team that identified and reconstructed the extinct 1918 virus, using traces unearthed in autopsy samples from World War I soldiers and from a victim buried in the Alaskan permafrost.

That misnamed Spanish flu “made all the world a killing zone,” wrote John M. Barry in “The Great Influenza: The Story of the Deadliest Pandemic in History.”

Historians think it started in Kansas in early 1918. By winter 1919, the virus had infected one-third of the global population and killed at least 50 million people, including 675,000 Americans. By comparison, the AIDS virus has claimed 35 million lives over four decades.

Three more flu pandemics have struck since, in 1957, 1968 and 2009, spreading widely but nowhere near as deadly. Taubenberger’s research shows the family tree, each subsequent pandemic a result of flu viruses carried by birds or pigs mixing with 1918 flu genes.

“This 100-year timeline of information about how the virus adapted to us and how we adapt to the new viruses, it teaches us that we can’t keep designing vaccines based on the past,” said Dr. Barney Graham, deputy director of NIH’s Vaccine Research Center.

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The new vaccine quest starts with two proteins, hemagglutinin and neuraminidase, that coat flu’s surface. The “H” allows flu to latch onto respiratory cells and infect them. Afterward, the “N” helps the virus spread.

They also form the names of influenza A viruses, the most dangerous flu family. With 18 hemagglutinin varieties and 11 types of neuraminidase — most carried by birds — there are lots of potential combinations. That virulent 1918 virus was the H1N1 subtype; milder H1N1 strains still circulate. This winter H3N2, a descendent of the 1968 pandemic, is causing most of the misery.

Think of hemagglutinin as a miniature broccoli stalk. Its flower-like head attracts the immune system, which produces infection-blocking antibodies if the top is similar enough to a previous infection or that year’s vaccination.

But that head also is where mutations pile up.

A turning point toward better vaccines was a 2009 discovery that, sometimes, people make a small number of antibodies that instead target spots on the hemagglutinin stem that don’t mutate. Even better, “these antibodies were much broader than anything we’ve seen,” capable of blocking multiple subtypes of flu, said Scripps’ Wilson.

Scientists are trying different tricks to spur production of those antibodies.